Black men suffer disproportionately from prostate cancer, both in terms of incidence and mortality, compared with their white counterparts. However, a newer study conducted by investigators at the University of California, San Francisco, and Dana-Farber Cancer Institute, Boston, found that black men have up to twice the risk of dying of low-risk prostate cancer than other racial and ethnic groups.¹ The ASCO Post spoke with the study’s first author, ­Brandon A. Mahal, MD, of the Department of Radiation Oncology, Harvard Medical School, Boston, about these findings and their clinical implications moving forward.

Brandon A. Mahal, MD

Racial Disparities in the Low-Risk Setting

We know that black men are more likely to develop high-grade, potentially lethal prostate cancers than their white counterparts. Did your study unearth anything that might describe this clinical disparity?

There is a great debate over whether prostate cancer disparities are driven by differences in factors inherent to prostate cancer itself vs nontumor factors (such as socioeconomic status, access to care, quality of care, and treatment pattern dissimilarities). Thus, we sought to address some of these questions by examining the risk of prostate cancer death by Gleason score in black and nonblack men from a large database of patients including over 200,000 men (over 30,000 black men) diagnosed with prostate cancer from 2010 to 2015 in the United States.

We found that after adjusting for the impact of socioeconomic status on prostate cancer outcomes, there was no observed disparity between black and nonblack men with Gleason 7 to 10 disease. This finding demonstrated the significant influence that socioeconomic status may have on previously observed and reported prostate cancer disparities, given that these disparities were no longer observed after taking this variable’s contribution to prostate cancer death into account.

“Increasing efforts are needed to study the drivers of disparities in the low-risk setting.”

— Brandon A. Mahal, MD

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We also found that black men with Gleason 6 disease appeared to have a higher risk of dying of prostate cancer than nonblack men, even after we adjusted for socioeconomic status. This finding was the first to show the possible interaction between Gleason score and race, suggesting that disparities in outcome may be driven by differences in lower-risk disease, rather than higher-risk disease. This is important because most efforts to address disparities have been focused on more aggressive and advanced cancers. Our findings suggest that increasing efforts are needed to study the drivers of disparities in the low-risk setting. Furthermore, these findings have potential implications for possible trial design.

Controversy Over How Best to Manage Gleason 6 Disease

Many experts strongly believe that a Gleason 6 finding should be considered a pseudocancer and that labeling it as cancer has historically caused unnecessary overtreatment. How does this clinical opinion fit in with your study findings?

There are multiple lines of evidence suggesting that Gleason 6 disease, when coupled with other low-risk features such as low prostate-specific antigen (PSA) level and early clinical tumor stage, is associated with a favorable prognosis, with a prostate cancer–specific survival rate of approximately 98% with long-term follow-up. Furthermore, there is strong evidence to suggest that treatment of low-risk Gleason 6 disease with either surgery or radiotherapy does not improve overall survival, although treatment appears to reduce the risk of metastases and potential subsequent need of lifelong hormone therapy.

However, low-risk trials have included few black men (typically less than 1% to 3%), but there has been evidence² that black men initially diagnosed with very low–risk Gleason 6 disease have a greater than three times risk of adverse features after surgery than other men. In this setting, how best to manage black men with low-risk or Gleason 6 disease is controversial. National guidelines urge caution when suggesting active surveillance for black men. It’s worth noting that active surveillance is a less-utilized strategy for black men than for men of other races in the United States.³

Our study was inspired, in part, by the controversy over managing Gleason 6 disease in black men. We demonstrated that black men with Gleason 6 disease were twice as likely to experience rare prostate cancer death relative to nonblack men. Although the death rates were low, we confirmed the disparities persisted, with higher death rates in a cohort with longer follow-up (2.2% vs 1.4%). This finding suggests that the small absolute difference in the risk of prostate cancer may increase over time with longer follow-up and more time for events (prostate cancer deaths are not necessarily expected until after longer follow-up in this setting).

An important epidemiologic point is that even if the differences in our study remained small, they could translate into large population-level disparities. Particularly, black men in 

the United States are 76% more likely to develop prostate cancer than white men.4 At the population level, the annual incidence of localized Gleason 6 disease in black men is approximately 66 per 100,000 persons compared with 45 per 100,000 for white men. Therefore, even a small absolute difference in the risk of prostate cancer death is magnified by the higher incidence rate in black men at the population level. We did not have space in our article to elaborate on this point, which may be easy to overlook and not immediately intuitive.

Furthermore, our findings could have been driven by more underascertainment of higher risk disease in black men at the time of biopsy, or possibly by the fact that low-grade prostate cancer may be distinct in black men. Additional factors, including differences in access to care or other systemic or socioeconomic issues that the database was not able to capture, may explain these findings.

Ultimately, our results highlight the need for further study to characterize low-grade disease in black men. They also indicate the need to determine the optimal treatment approach, including whether active surveillance is equally efficacious in black men as in their white counterparts.

PSA Screening in Black Men

The value of the PSA test has been debated for decades. Do you support PSA screening in black men?

This is a great question that was not directly examined by this study. The U.S. Preventive Services Task Force (USPSTF) acknowledges that black men may derive greater benefit from PSA screening; however, the USPSTF cannot make specific recommendations regarding PSA screening based on race because of the lack of randomized trial evidence. That said, the USPSTF suggests informed decision-making conversations between black men and their providers about the potentially higher risk of developing prostate cancer.

“Combining multiple lines of evidence with logical reasoning tells us that PSA testing can be particularly beneficial for black men and therefore should be recommended for appropriate men.”

— Brandon A. Mahal, MD

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However, considering the evidence from randomized trials alongside epidemiologic studies, we can reasonably ascertain that PSA screening would be of greater benefit to black men than to men of other races. Ultimately, I think that combining multiple lines of evidence with logical reasoning tells us that PSA testing can be particularly beneficial for black men and therefore should be recommended for appropriate men.

Closing Thoughts

Please share any concluding thoughts on this issue.

We have known about prostate cancer disparities for decades, and current research is beginning to untangle some of the drivers of disparities and identify in what subgroups they might exist. However, the problem is complex, and the answers will be multifactorial. It will take a concerted effort among social scientists, epidemiologists, urologists, clinical biologists, and clinical researchers. Perhaps most important, to make progress in this area, our clinical trials need to accrue representative populations of black men. Our study indicates that more research is necessary on the many clinical and socioeconomic factors that may make low-risk prostate cancer more deadly in black men. ■

DISCLOSURE: Dr. Mahal reported no conflicts of interest.

REFERENCES

1. Mahal BA, Berman RA, Taplin ME, et al: Prostate cancer–specific mortality across Gleason scores in black vs nonblack men. JAMA 320:2479-2481, 2018.

2. Sundi D, Ross AE, Humphreys EB, et al: African American men with very low-risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: Should active surveillance still be an option for them? J Clin Oncol 31:2991-2997, 2013.

3. Butler S, Muralidhar V, Chavez J, et al: Active surveillance for low-risk prostate cancer in black patients. N Engl J Med 380:2070-2072, 2019.

4. Siegel RL, Miller KD, Jemal A: Cancer statistics, 2019. CA Cancer J Clin 69:7-34, 2019.